5-methoxy-2-methylsulfinyl-1H-benzimidazole | 135429-78-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-methoxy-2-methylsulfinyl-1H-benzimidazole
• 英文别名: 6-methoxy-2-methylsulfinyl-1H-benzimidazole
• CAS: 135429-78-6
• 化学式: C₉H₁₀N₂O₂S
• 分子量: 210.257
• InChiKey: WWEMNCUDSJJANZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-methylsulfinyl-1H-benzimidazole 在 氢溴酸 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 六甲基磷酰三胺 、 乙醇 、 氯仿 、 乙腈 为溶剂， 反应 7.5h， 生成 (S)-2-Amino-4-methyl-pentanoic acid [2-(5-methoxy-1H-benzoimidazole-2-sulfinyl)-phenyl]-amide
  参考文献：
  名称：

  Amino acid amides of 2-[(2-aminobenzyl)sulfinyl]benzimidazole as acid-stable prodrugs of potential inhibitors of H+K+ ATPase

  摘要：

  A series of amino acid amides of 2-[(2-aminobenzyl)sulfinyl]benzimidazole were prepared and found to possess gastric antisecretory activity on oral administration. (Glycylaminobenzyl)sulfinyl compound 23a, stable in artificial gastric juice (pH 1.2), was given orally to dogs. It was absorbed efficiently and converted into aniline derivative 7a which showed a very high plasma concentration. Compound 23a was hydrolyzed by the action of aminopeptidase present in plasma or the brush border fraction of the small intestine to release the terminal glycine. omicron-Aniline derivatives showed good activity in in vitro H+/K+-ATPase inhibition as well as in the inhibition of histamine stimulated acid secretion in isolated bullfrog gastric mucosa. Although these omicron-aniline derivatives showed no or weak gastric antisecretory activity in rat by id administration, they were active when administered ip. Therefore, these amino acid amides were considered to be acid stable prodrugs of proton pump inhibiting omicron-aniline derivatives. The mechanism of H+/K+-ATPase inhibition of 7a was also examined.

  DOI：

  10.1016/0223-5234(91)90024-h
• 作为产物：
  描述：

  5-甲氧基-2-(甲基硫代)苯并咪唑 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 以73.7%的产率得到5-methoxy-2-methylsulfinyl-1H-benzimidazole
  参考文献：
  名称：

  质子泵抑制剂对胃 (H+, K+)-ATPase 的共价抑制化学

  摘要：

  质子泵抑制剂 (PPI) 是广泛用于治疗酸相关疾病的药物，是取代的吡啶基甲基亚磺酰基苯并咪唑或咪唑并吡啶衍生物。它们都是通过酸激活反应性亲硫体来抑制胃分泌酸 (H(+), K(+))-ATPase 的前药，这些亲硫体与一个或多个可从酶的外质表面接触的半胱氨酸形成二硫键。这种独特的酸催化机制归因于吡啶环的亲核性。然而，此处获得的数据表明，它们向反应性阳离子亲硫磺酸或次磺酰胺的转化主要不依赖于吡啶质子化，而是依赖于咪唑组分的第二次质子化，这增加了咪唑上 C-2 位的亲电性。这种质子化导致 C-2 与吡啶环的未质子化部分反应形成反应性衍生物。相关的 PPI pK(a) 由苯并咪唑或咪唑并吡啶亚磺酰基甲基部分在不同介质 pH 值下的紫外光谱测定。相对酸稳定的类似物 N(1)-甲基兰索拉唑 (6b) 的合成允许直接测定该完整 PPI 的两个 pK(a) 值，从而可以计算所有 PPI 的两个 pK(a)

  DOI：

  10.1021/ja049607w

文献信息

• Amino acid amides of 2-[(2-aminobenzyl)sulfinyl]benzimidazole as acid-stable prodrugs of potential inhibitors of H+K+ ATPase
  作者：K Hirai、H Koike、T Ishiba、S Ueda、I Makino、H Yamada、T Ichihashi、Y Mizushima、M Ishikawa、Y Ishihara、Y Hara、H Hirose、N Shima、M Doteuchi

  DOI：10.1016/0223-5234(91)90024-h

  日期：1991.3

  A series of amino acid amides of 2-[(2-aminobenzyl)sulfinyl]benzimidazole were prepared and found to possess gastric antisecretory activity on oral administration. (Glycylaminobenzyl)sulfinyl compound 23a, stable in artificial gastric juice (pH 1.2), was given orally to dogs. It was absorbed efficiently and converted into aniline derivative 7a which showed a very high plasma concentration. Compound 23a was hydrolyzed by the action of aminopeptidase present in plasma or the brush border fraction of the small intestine to release the terminal glycine. omicron-Aniline derivatives showed good activity in in vitro H+/K+-ATPase inhibition as well as in the inhibition of histamine stimulated acid secretion in isolated bullfrog gastric mucosa. Although these omicron-aniline derivatives showed no or weak gastric antisecretory activity in rat by id administration, they were active when administered ip. Therefore, these amino acid amides were considered to be acid stable prodrugs of proton pump inhibiting omicron-aniline derivatives. The mechanism of H+/K+-ATPase inhibition of 7a was also examined.
• Chemistry of Covalent Inhibition of the Gastric (H⁺, K⁺)-ATPase by Proton Pump Inhibitors
  作者：Jai Moo Shin、Young Moon Cho、George Sachs

  DOI：10.1021/ja049607w

  日期：2004.6.1

  either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives. They are all prodrugs that inhibit the acid-secreting gastric (H(+), K(+))-ATPase by acid activation to reactive thiophiles that form disulfide bonds with one or more cysteines accessible from the exoplasmic surface of the enzyme. This unique acid-catalysis mechanism had been ascribed to the nucleophilicity of the

  质子泵抑制剂 (PPI) 是广泛用于治疗酸相关疾病的药物，是取代的吡啶基甲基亚磺酰基苯并咪唑或咪唑并吡啶衍生物。它们都是通过酸激活反应性亲硫体来抑制胃分泌酸 (H(+), K(+))-ATPase 的前药，这些亲硫体与一个或多个可从酶的外质表面接触的半胱氨酸形成二硫键。这种独特的酸催化机制归因于吡啶环的亲核性。然而，此处获得的数据表明，它们向反应性阳离子亲硫磺酸或次磺酰胺的转化主要不依赖于吡啶质子化，而是依赖于咪唑组分的第二次质子化，这增加了咪唑上 C-2 位的亲电性。这种质子化导致 C-2 与吡啶环的未质子化部分反应形成反应性衍生物。相关的 PPI pK(a) 由苯并咪唑或咪唑并吡啶亚磺酰基甲基部分在不同介质 pH 值下的紫外光谱测定。相对酸稳定的类似物 N(1)-甲基兰索拉唑 (6b) 的合成允许直接测定该完整 PPI 的两个 pK(a) 值，从而可以计算所有 PPI 的两个 pK(a)